Bioengineering Annulus Fibrosus using Silk Scaffold

使用丝支架的生物工程纤维环

• 批准号: 7140307
• 负责人: RITA A KANDEL
• 金额: $ 12.76万
• 依托单位: SINAI HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140307
• 关键词: SDS polyacrylamide gel electrophoresis; autoradiography; biodegradable product; bioengineering /biomedical engineering; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; bioreactors; biotechnology; intervertebral disk; polymerase chain reaction; regeneration; spine disorder; tissue support frame

DESCRIPTION (provided by applicant): Degenerative intervertebral disc disease is a very common problem and currently there is no optimal treatment for individuals who develop persistent back disease as a result of this disease. Although back pain is rarely life-threatening, the annual cost in terms of lost productivity, medical expenses and workers' compensation benefits was estimated at $50 billion in 1998 in the United States. The long term goal of our research is to generate using a bioengineering approach a spinal unit in vitro that has tissue, which structurally and functionally approaches that of a natural intervertebral disc and is suitable as replacement for a damaged disc. Additionally this model can be used to investigate mechanisms regulating disc tissue formation, maintenance, and degeneration in vitro to identify new ways to regenerate disc tissue or new therapeutic agents to treat or prevent the disease. Our immediate aim is to develop a model of a spinal unit consisting of intervertebral disc tissue and cartilage endplate formed on and anchored into a porous bone substitute material. The specific aims of this proposal are: 1) To design a porous biodegradable polymeric scaffold made of silk with an organization to allow guided tissue formation to mimic the in vivo annulus fibrosus organization. 2) To form annulus fibrosus tissue in vitro, utilizing the silk scaffold. Annulus fibrosus cells will be seeded into the scaffold. The cells will be allowed to form tissue in a bioreactor in the presence or absence of a mechanical force (compression and/or shear). An optimal loading regime defined by amplitude and duration offeree application will be determined and the effect of this in vitro mechanical stimulation on tissue composition, collagen organization, and mechanical properties will be determined. 3) To generate a model of portion of a spinal unit composed of in vitro-formed annulus fibrosus tissue surrounding the nucleus pulposus, cartilage integrated with the top surface of a bone substitute (calcium polyphosphate). The viability and mechanical properties of the tissue will be evaluated.

描述（由申请人提供）：退行性椎间盘疾病是一个非常常见的问题，目前对于因这种疾病而发展为持续性背部疾病的个体还没有最佳的治疗方法。尽管背痛很少危及生命，但 1998 年美国每年因生产力损失、医疗费用和工人赔偿福利而造成的损失估计为 500 亿美元。我们研究的长期目标是利用生物工程方法在体外生成具有组织的脊柱单元，该脊柱单元在结构和功能上接近天然椎间盘，并且适合作为受损椎间盘的替代品。此外，该模型还可用于研究体外调节椎间盘组织形成、维持和退化的机制，以确定椎间盘组织再生的新方法或治疗或预防疾病的新治疗剂。我们的近期目标是开发一种脊柱单元模型，该模型由形成并固定在多孔骨替代材料上的椎间盘组织和软骨终板组成。该提案的具体目标是：1）设计一种由丝制成的多孔可生物降解聚合物支架，其组织允许引导组织形成来模拟体内纤维环组织。 2）利用丝支架在体外形成纤维环组织。纤维环细胞将被接种到支架中。在存在或不存在机械力（压缩和/或剪切）的情况下，细胞将被允许在生物反应器中形成组织。将确定由受供者应用的幅度和持续时间定义的最佳加载方案，并将确定这种体外机械刺激对组织成分、胶原蛋白组织和机械性能的影响。 3) 生成由体外形成的围绕髓核、软骨和骨替代物（聚磷酸钙）顶面的纤维环组织组成的脊柱单元部分模型。将评估组织的活力和机械性能。